Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice

• Main Authors: Wei-Lin Lo, Shih-Wei Lo, Su-Jung Chen, Ming-Wei Chen, Yuan-Ruei Huang, Liang-Cheng Chen, Chih-Hsien Chang, Ming-Hsin Li
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: International Journal of Molecular Sciences
• Subjects: ¹¹¹In-DOTA-EB-cRGDfK; indium-111; nanoSPECT/CT; pharmacokinetics
• Online Access: https://www.mdpi.com/1422-0067/22/11/5459
• ISSN: 1661-6596; 1422-0067

The Arg–Gly–Asp (RGD) peptide shows a high affinity for α_vβ₃ integrin, which is overexpressed in new tumor blood vessels and many types of tumor cells. The radiolabeled RGD peptide has been studied for cancer imaging and radionuclide therapy. We have developed a long-term tumor-targeting peptide DOTA-EB-cRGDfK, which combines a DOTA chelator, a truncated Evans blue dye (EB), a modified linker, and cRGDfK peptide. The aim of this study was to evaluate the potential of indium-111(¹¹¹In) radiolabeled DOTA-EB-cRGDfK in α_vβ₃ integrin-expressing tumors. The human glioblastoma cell line U-87 MG was used to determine the in vitro binding affinity of the radiolabeled peptide. The in vivo distribution of radiolabeled peptides in U-87 MG xenografts was investigated by biodistribution, nanoSPECT/CT, pharmacokinetic and excretion studies. The in vitro competition assay showed that ¹¹¹In-DOTA-EB-cRGDfK had a significant binding affinity to U-87 MG cancer cells (IC₅₀ = 71.7 nM). NanoSPECT/CT imaging showed ¹¹¹In-DOTA-EB-cRGDfK has higher tumor uptake than control peptides (¹¹¹In-DOTA-cRGDfK and ¹¹¹In-DOTA-EB), and there is still a clear signal until 72 h after injection. The biodistribution results showed significant tumor accumulation (27.1 ± 2.7% ID/g) and the tumor to non-tumor ratio was 22.85 at 24 h after injection. In addition, the pharmacokinetics results indicated that the ¹¹¹In-DOTA-EB-cRGDfK peptide has a long-term half-life (T_1/2_λ_z = 77.3 h) and that the calculated absorbed dose was safe for humans. We demonstrated that radiolabeled DOTA-EB-cRGDfK may be a promising agent for glioblastoma tumor imaging and has the potential as a theranostic radiopharmaceutical.